i) Field of the Invention
This invention relates to a process for producing an entrapped or microencapsulated drug, more especially a process employing in vitro synthesis of a polyhydroxyalkanoate homopolymer or copolymer.
ii) Description of Prior Art Poly(hydroxyalkanoates), PHA, are biopoly(.beta.-hydroxyalkanoate)-esters which are produced by microorganisms. The general pathways of PHA biosynthesis are well known. The poly(.beta.-hydroxybutyrate) (PHB) biosynthetic pathway uses acetyl-CoA which generates [R]-(-)-3-hydroxybutyryl-CoA as the natural monomer. This monomer responds to the naturally produced polymerase enzyme which rapidly produces PHB.
Processes have been proposed for encapsulating drugs within a polyhydroxyalkanoate shell. These processes typically require use of organic solvents, see for example Bissery et al, Microspheres and Drug Therapy Pharmaceutical, Immunological and Medical Aspects, edited by S. S. Davis et al, Elsevier Science, pp. 217-227, 1984; Juni et al Journal of Controlled Release, 4, 25-32, 1986; and Kawaguchi et al, Journal of Pharmaceutical Sciences, 81, 508-512, 1992. Use of polyhydroxyalkanoates in the entrappment or microencapsulation of drugs is especially advantageous since these polymers are biodegradable, non-toxic and otherwise non-harmful when administered to a living body.
It would be desirable to provide new entrappment or encapsulation processes employing non-toxic, biodegradable polymers, especially polymers that can be formed in situ in the entrappment or encapsulation of the drug.